The recent finding of conformational changes in the muscle protein actin suggests a more dynamic role for actin in contractile events. This proposed research will investigate the occurrence of conformational changes in actin both during its polymerization and while it is in the polymer state, and will study the interaction of the various conformational states of actin with heavy meromyosin (HMM) and subfragment I (S-I). Actin will be characterized by its rate of proteolytic digestion, analysis of the digestion products, viscosity, and changes in ultraviolet absorption. This approach has already provided evidence for an F-monomer state and also for what appears to be a newly-detected intermediate state called oligomeric actin. After characterizing the equilibrium conformational states in the polymerization of actin, conditions will be altered so that the rate of their formation and/or disappearance can be studied. To examine the possibility of conformational changes in the intact polymer, measurements will be made in the presence of various agents which are known to affect the stability of the polymer. Both the binding of the various conformational states of actin to HMM and S-I and their ability to activate the Mg ions-ATPase of these myosin fragments will be studied. Moreover, determinations will be made of the ability of the digestion products from the various conformational states to polymerize, or to remain polymerized, to retain bound nucleotide, and to interact with HMM and S-I. While this research will not help clarify the changes which must occur in the structure of G-actin so that it is capable of interacting with myosin, and also provide some understanding of the possible conformational changes that can occur in the F-actin molecule, the increase in knowledge about the G to F transformation may well have great importance in non-muscle motile systems where monomer-polymer transitions are thought to play a major role in motile events.